Month: June 2024

Visual Cortex Stimulation Boosts Brain-computer Interface

Deep brain stimulation illustration. Credit: NIH

Brain-computer interfaces, or BCIs, promise life-changing benefits for people suffering from a range of neurological conditions, but implementation is for both the invasive and noninvasive methods is challenging. Researchers led by Bin He at Carnegie Mellon University used an innovative electroencephalogram (EEG) wearable. They successfully integrated a novel focused ultrasound stimulation to realise bidirectional BCI that both encodes and decodes brain waves using machine learning in a study with 25 human subjects.

This work, published in Nature Communicationsopens up a new avenue to significantly enhance not only the signal quality, but also, overall nonivasive BCI performance by stimulating targeted neural circuits.

Noninvasive BCI is lauded for its merits of being cheap, safe, and virtually applicable to everyone, but because signals are recorded over the scalp versus inside the brain, low signal quality presents some limitations. The He group is exploring ways to improve the effectiveness of noninvasive BCIs and, over time, has used deep learning approaches to decode what an individual was thinking and then facilitate control of a cursor or robotic arm.

In their latest research, the He group demonstrated that through precision noninvasive neuromodulation using focused ultrasound, the performance of a BCI could be improved for communication.

“This paper reports a breakthrough in noninvasive BCIs by integrating a novel focused ultrasound stimulation to realise bidirectional BCI functionality,” explained Bin He, professor of biomedical engineering at Carnegie Mellon University. “Using a communication prosthetic, 25 human subjects spelled out phrases like ‘Carnegie Mellon’ using a BCI speller. Our findings showed that the addition of focused ultrasound neuromodulation significantly boosted the performance of EEG-based BCI. It also elevated theta neural oscillation that enhanced attention and led to enhanced BCI performance.”

For context, a BCI speller is a 6×6 visual motion aide containing the entire alphabet that is commonly used by nonspeakers to communicate. In He’s study, subjects donned an EEG cap and just by looking at the letters, were able to generate EEG signals to spell the desired words. When a focused ultrasound beam was applied externally to the V5 area (part of the visual cortex) of the brain, the performance of the noninvasive BCI greatly improved among subjects. The neuromodulation-integrated BCI actively altered the engagement of neural circuits to maximize the BCI performance, compared to previous uses, which consisted of pure processing and decoding recorded signals.

Following this discovery, the He lab is further investigating the merits and applications of focused ultrasound neuromodulation to the brain, beyond the visual system, to enhance noninvasive BCIs. They also aim to develop more compact-focused ultrasound neuromodulation device for better integration with EEG-based BCIs, and to integrate AI to continue to enhance the overall system performance.

“This is my lifelong interest, and I will never give up,” emphasized He. “Working to improve noninvasive technology is difficult, but I strongly believe that if we can find a way to make it work, everyone will benefit. I will keep working, and someday, noninvasive lifesaving technology will be available for every household.

Source: College of Engineering, Carnegie Mellon University

Discovery Health says Road Accident Fund in Breach of Court Order

Photo by Bill Oxford on Unsplash

By Tania Broughton

Discovery Health had an “overwhelming case” against the Road Accident Fund (RAF) and its CEO Collins Letsoalo showing it was clearly in breach of a 2022 court ruling that the fund was not allowed to withhold payments for past medical expenses from road accident victims who had been paid out by their medical schemes.

This was the submission of Advocate Wim Trengove, on behalf of Discovery, at a special court hearing seeking to hold the fund and Letsoalo to account.

While initially Discovery, in its application before Gauteng Judge President Dunstan Mlambo and judges Ingrid Opperman and Noluntu Bam on Thursday, were seeking orders of contempt of court, Trengrove said it was now only seeking an order of “breach” and to compel compliance.

He said this would give Letsoalo a further opportunity to “have his say” as to why he should not be found in contempt and possibly jailed for it.

In 2022, Judge Mandla Mbongwe ruled in the Pretoria High Court that a new directive – effectively refusing to pay for past medical expenses of those claimants already paid out by medical aids – was unlawful.

The RAF was unsuccessful in its appeals to both the Supreme Court of Appeal and the Constitutional Court.

Read the original Pretoria High Court judgment here

Trengove argued that the RAF had continued to implement the directive, regardless of the court ruling.

“We have a list of about 20 cases, all of which are in line with the Mbongwe judgment,” he said.

After the apex court refused to grant the RAF leave to appeal the Mbongwe judgment, two further “directives” came to light in which the fund seemingly sought to side-step the legal implications of the Mbongwe judgment.

Trengove said “directive two” was also raised once in litigation and was rejected. Under this directive, the fund had argued that it should not have to compensate medically insured victims if they had been paid out in accordance with prescribed minimum benefits.

“Then it produced ‘directive three’ which is equally spurious,” he said.

This was based on a section of the RAF Act, which prohibited compensation to anyone who had agreed to share compensation with another person. The fund argued that the agreement between a medical scheme and its members fell foul of this.

“But that agreement is merely an agreement to avoid double-compensation. That the medical aid pays upfront and if the member recovers (from the fund), then that member will reimburse the medical aid,” Trengove said.

He said regardless, the new directive did not absolve the fund from complying with the Mbongwe ruling.

That ruling, he said, confirmed that a claim against the fund is a claim in delict: the fund steps into the shoes of the wrongdoer, and “the perpetrator is not entitled to benefit from the insurance proceeds of the victim”.

“Our courts have held that medical schemes, for the purposes of claims, are akin to insurance, and claims cannot be taken into account when determining the quantum of liability,” Trengove said.

RAF denial

But advocate Cedric Puckrin, who appeared with advocate Gerhard Cilliers for the fund, said Trengove had argued his case “with rose-coloured glasses”.

Cilliers said the fund was entitled to implement the first directive during the period when the appeal process had been underway.

He said Discovery was arguing a new case, not an enforcement of the Mbongwe ruling, and had based it on ten examples where the fund had responded to letters of demand by claimants, indicating that it would dispute liability for any claim for past medical expenses.

Cilliers suggested that Discovery had no standing in court, and that it was up to individual claimants to take their matters to court.

He also said the ten examples did not show that the fund was in breach.

“It is not Discovery’s case that RAF is enforcing the 2022 directive. It wants you to go further and ask you to find that the subsequent directives are the same. And we submit that is not the proper process to follow. It is an abuse of the process.”

Advocate Puckrin argued that while the third directive might be “entirely wrong”, it was a different directive which could only be set aside by a separate application to the court.

He said it could not be considered a “breach” of the Mbongwe judgment.

But Judge Opperman suggested that it was just a “new piece of paper” dealing with the same issue.

“But it’s based on a new principle,” Puckrin said. “It’s far more limited.”

In reply, Trengove said the Mbongwe judgment has set out a statement of “general principle” that the fund could not free itself from paying full compensation to medical aid members.

He said Letsoalo and other fund officials had made a series of public statements which reflected their “unlawful disdain” for the ruling.

“A delinquent public body cannot insulate itself against compliance with a court order by adopting a directive in effect not to comply with it. It is contrary to the rule of law.”

Judgment was reserved.

Republished from GroundUp  under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Read the original article

Walking is Highly Effective for Stopping Low Back Pain from Returning

Photo by Henry Xu on Unsplash

New research from Macquarie University’s Spinal Pain Research Group shows that walking has the potential to change the way low back pain is managed, making effective interventions accessible to more people than ever before. The results of the trial, which combined walking with education, are published in The Lancet.

About 800 million people worldwide have low back pain, which is a leading cause of disability and reduced quality of life. Recurrences of low back pain are very common, with seven in 10 people who recover from an episode going on to have a recurrence within a year.

Professor of Physiotherapy Mark Hancock and his research team have been investigating ways to shift the emphasis from treatment to prevention to improve the management of back pain, an approach that empowers individuals to manage their own health and reduces the cost to society and the healthcare system.

Far from the bed rest recommended for back pain in the past, current best practice includes the combination of exercise and education, both to treat current pain and to prevent future episodes.

While beneficial, some forms of exercise are not accessible or affordable to many people due to their high cost, complexity and need for supervision.

A simpler, more accessible method

The world-first WalkBack trial examined whether a programme of walking combined with education could be effective in preventing recurrences of low back pain.

The trial followed 701 adults who had recently recovered from an episode of low back pain, randomly allocating participants to either an individualised walking program facilitated by a physiotherapist and six education sessions across six months, or to a no-intervention control group.

The participants’ progress was then followed for between one and three years to collect information about any new recurrences of low back pain they experienced.

The researchers’ primary aim was to compare the two groups for the number of days before participants experienced a recurrence of back pain that impacted daily activities or required care from a healthcare provider.

They also evaluated the cost effectiveness of the intervention, including costs related to work absenteeism and healthcare services.

Longer pain-free periods

The paper’s senior author, Professor Hancock, says what they discovered could have a profound impact on how low back pain is managed.

“The intervention group had fewer occurrences of activity-limiting pain compared to the control group, and a longer average period before they had a recurrence, with a median of 208 days compared to 112 days,” Professor Hancock says. “The risk of having a recurrence that required seeking care was nearly halved in those in the intervention group.

“Walking is a low-cost, widely accessible and simple exercise that almost anyone can engage in, regardless of age, geographic location or socio-economic status.

“We don’t know exactly why walking is so good for preventing back pain, but it is likely to include the combination of gentle oscillatory movements, loading and strengthening the spinal structures and muscles, relaxation and stress relief, and the release of ‘feel-good’ endorphins.

“And of course, we also know that walking comes with many other health benefits, including cardiovascular health, improved bone density, maintenance of a healthy weight and improved mental health.”

Professor Hancock said the amount of walking each person completed was individualised based on a range of factors including their age, physical capacity, preferences and available time. Participants were given a rough guide to build up to 30 minutes, five times a week over a six-month period.

After three months, Professor Hancock said most of the people who took part were walking three to five days a week for an average of 130 minutes.

“You don’t need to be walking five or 10 kilometres every day to get these benefits,” Professor Hancock says.

A cost-effective option

The paper’s lead author, Postdoctoral Fellow Dr Natasha Pocovi, says in addition to providing participants with longer pain-free periods, they found the program was also cost effective.

“It not only improved people’s quality of life, but it reduced their need both to seek healthcare support and the amount of time taken off work by approximately half,” Dr Pocovi says.

“The exercise-based interventions to prevent back pain that have been explored previously are typically group-based and need close clinical supervision and expensive equipment, so they are much less accessible to the majority of patients.

“Our study has shown that this effective and accessible means of exercise has the potential to be successfully implemented on a much larger scale than other forms of exercise.”

To build on these findings, the team now hopes to explore how they can integrate the preventive approach into the routine care of patients who experience recurrent low back pain.

Source: MacQuarie University

Gut Bacteria Enzymes to Turn Donated A and B Blood Universal

Photo by Charliehelen Robinson on Pexels

The quest to develop universal donor blood has taken a decisive step forward. Researchers in Denmark have discovered enzymes that, when mixed with red blood cells, are able to remove specific sugars that make up the A and B antigens in the human AB0 blood groups. The results appear in Nature Microbiology.

“For the first time, the new enzyme cocktails not only remove the well-described A and B antigens, but also extended variants previously not recognised as problematic for transfusion safety. We are close to being able to produce universal blood from group B donors, while there is still work to be done to convert the more complex group A blood. Our focus is now to investigate in detail if there are additional obstacles and how we can improve our enzymes to reach the ultimate goal of universal blood production,” says Professor Maher Abou Hachem, who is the study leader at Technical University Denmark (DTU) and one of the senior scientists behind the discovery.

He states that the discovery is the result of combining the expertise of DTU researchers in enzymes from the human gut microbiota and Lund University researchers in carbohydrate-based blood groups and transfusion medicine.

High demand for donor blood

Human red blood cells carry specific complex sugars structures (antigens) that define the four AB0 blood groups A, B, AB and 0. These antigens control compatibility between donors and recipients for safe blood transfusion and organ transplantation. Donor blood is screened for disease markers and the main blood groups. It can then be stored refrigerated for up to 42 days.

The need for donor blood is high due to the elderly making up a larger proportion of the population and more patients undergoing blood-intensive medical procedures. Successfully converting A or B blood types into AB0 universal donor blood can markedly reduce the logistics and costs currently associated with storing four different blood types. In addition, the development of universal donor blood will lead to an increased supply of donor blood by reducing the waste of blood approaching its expiry date.

The reason why it is necessary to remove the A and B antigens to create universal donor blood is because they can trigger life-threatening immune reactions when transfused into non-matched recipients.

The concept of using enzymes to generate universal donor blood was introduced more than 40 years ago. Since then, higher efficiency enzymes to remove the A and B antigens were discovered, but researchers are still not able to explain or abolish all immune reactions related to the blood, and therefore these enzymes are still not used in clinical practice.

Enzymes from the gut

The research groups from DTU and Lund University have gone new ways to find enzymes that can remove both the A and B blood antigens and the sugars that block them. The research teams discovered new mixtures of enzymes from the human gut bacterium Akkermansia muciniphila that feeds by breaking down the mucus, which covers the surface of the gut. It turns out that these enzymes are exceptionally efficient, as the complex sugars at the surface of the intestinal mucosa share chemical resemblance with those found at the surface of blood cells.

“What is special about the mucosa is that bacteria, which are able to live on this material, often have tailor-made enzymes to break down mucosal sugar structures, which include blood group AB0 antigens. This hypothesis turned out to be correct,” says Maher Abou Hachem.

The researchers in this study tested 24 enzymes, which they used to process hundreds of blood samples.

“Universal blood will create a more efficient utilisation of donor blood, and also avoid giving AB0-mismatched transfusions by mistake, which can otherwise lead to potentially fatal consequences in the recipient. When we can create AB0-universal donor blood, we will simplify the logistics of transporting and administering safe blood products, while at the same time minimizing blood waste” says Professor Martin L. Olsson, the leader of the study at Lund University.

The researchers from DTU and Lund University have applied for a patent on the new enzymes and the method for enzyme treatment and expect to make further progress on this in their new joint project over the next three and a half years. If successful, the concept needs to be tested in controlled patient trials before this can be considered for commercial production and clinical use.

The initial research project is funded by the Independent Research Fund Denmark (Technology and Production Sciences, FTP), the Swedish Research Council, ALF grants from the Swedish government and county councils as well as the Knut and Alice Wallenberg Foundation and Research Fund Denmark, Natural Sciences, FNU), while the new continued project is funded by the Novo Nordisk Foundation, Interdisciplinary Synergy Programme.

The AB0 blood group antigens found on the surface of red blood cells are also found on the mucosal layer that lines the surface of the gut. Researchers have harnessed a specialised human gut bacterium and its ability to use these antigens as nutrients to discover and develop two enzyme mixtures that convert group A and B red blood cells into universal donor blood. Graphic: Mathias Jensen, postdoc at DTU.

About Akkermansia muciniphila

Akkermansia muciniphila is a bacterium found abundantly in the guts of most healthy humans. This bacterium can break down mucus in the gut and produces beneficial compounds such as the short-chain fatty acid propionate, in addition to exerting beneficial effects on body weight and metabolic markers.

Source: Technical University of Denmark

Study Trials First Drug Therapy for Sleep Apnoea

Photo by Ketut Subiyanto on Pexels

In an international phase III study, researchers have demonstrated the potential of tirzepatide, known to manage type 2 diabetes, as the first effective drug therapy for obstructive sleep apnoea (OSA), a sleep-related disorder characterised by repeated episodes of irregular breathing due to complete or partial blockage of the upper airway.

The results, published in the New England Journal of Medicine, highlight the treatment’s potential to improve the quality of life for millions around the world affected by OSA.

“This study marks a significant milestone in the treatment of OSA, offering a promising new therapeutic option that addresses both respiratory and metabolic complications,” said Atul Malhotra, MD, lead author of the study, professor of medicine at University of California San Diego School of Medicine and director of sleep medicine at UC San Diego Health.

OSA can result in reduced blood oxygen levels and can also be associated with an increased risk of cardiovascular complications, such as hypertension and heart disease. Recent studies, also led by Malhotra, suggest that the number of OSA patients worldwide is close to 936 million.

Conducted in two Phase III, double-blinded, randomised, controlled trials, the new study cohort recruited 469 participants from 9 countries with clinical obesity and living with moderate-to-severe OSA. Participants either used or did not use continuous positive airway pressure (CPAP) therapy, the most common sleep apnoea treatment which uses a machine to maintain an open airway during sleep, preventing interruptions in breathing. Patients were administered either 10 or 15mg of the drug by injection or a placebo and followed for 52 weeks.

Researchers found that tirzepatide led to a significant decrease in the number of breathing interruptions during sleep, a key indicator used to measure the severity of OSA. This improvement was much greater than what was seen in participants that were given a placebo. Importantly, some participants that took the drug reached a point where CPAP therapy might not be necessary. Considerable data suggest that a drug therapy that targets both sleep apnoea and obesity is beneficial rather than treating either condition alone.

Additionally, the drug therapy improved other aspects related to OSA, such as reducing the risk factors of cardiovascular diseases and improved body weight. The most common side effect reported was mild stomach issues.

“Historically, treating OSA meant using devices during sleep, like a CPAP machine, to alleviate breathing difficulties and symptoms,” Malhotra said. “However, its effectiveness relies on consistent use. This new drug treatment offers a more accessible alternative for individuals who cannot tolerate or adhere to existing therapies. We believe that the combination of CPAP therapy with weight loss will be optimal for improving cardiometabolic risk and symptoms. Tirzepatide can also target specific underlying mechanisms of sleep apnoea, potentially leading to more personalised and effective treatment.”

Malhotra adds that having a drug therapy for OSA represents a significant advancement in the field. 

“It means we can offer an innovative solution, signifying hope and a new standard of care to provide relief to countless individuals and their families who have struggled with the limitations of existing treatments,” said Malhotra. “This breakthrough opens the door to a new era of OSA management for people diagnosed with obesity, potentially transforming how we approach and treat this pervasive condition on a global scale.”

Next steps include conducting clinical trials to examine longer term effects of tirzepatide.

Source: Atrium Health Wake Forest Baptist

New Study Reveals Promising Drug Target for Osteoporosis Treatment

Photo by Mehmet Turgut Kirkgoz on Unsplash

In a recent study published in Journal of Cellular Physiology, researchers from Tokyo University of Science discovered a new target for the treatment of osteoporosis, which is responsible for 8.9 million fractures globally each year. They focused on improving a common bone-strengthening drug, teriparatide, which has a tendency to also increase bone resorption. By targeting a newly identified gene, they were able to suppress teriparatide’s bone resorption effect.

Induction of parathyroid hormone (PTH) signalling using the synthetic PTH-derived peptide – teriparatide, has demonstrated strong bone-promoting effects in patients with osteoporosis. These effects are mediated by osteogenesis, the process of bone formation involving the differentiation and maturation of bone-forming cells called osteoblasts. However, PTH induction is also associated with the differentiation of macrophages into osteoclasts, which resorb bone. Although, bone remodelling by osteoblasts and osteoclasts is crucial for maintaining skeletal health, PTH-induced osteoclast differentiation can decrease treatment efficacy in patients with osteoporosis. However, precise molecular mechanisms underlying the dual action of PTH signaling in bone remodelling are not well understood.

To bridge this gap, Professor Tadayoshi Hayata and Ms Chisato Sampei, from Tokyo University of Science, along with their colleagues, conducted a series of experiments to identify druggable target genes downstream of PTH signalling in osteoblasts. Explaining the rationale behind their study , corresponding author, Prof. Hayata says, “In Japan, it is estimated that 12.8 million people, or one in ten people, suffer from osteoporosis, which can significantly deteriorate their quality of life. Teriparatide is classified as a drug that promotes bone formation, but it also promotes bone resorption, which may limit bone formation. However, the full scope of its pharmacological action remains unknown.”

The researchers treated cultured mouse osteoblast cells and mice with teriparatide. They then assessed gene expression changes induced by PTH in both the cultured cells and bone cells isolated from the femurs of the treated animals, using advanced RNA-sequencing analysis. Among several upregulated genes, they identified a novel PTH-induced gene – ‘Gprc5a’, encoding an orphan G protein-coupled receptor, which has been previously explored as a therapeutic target. However, its precise role in osteoblast differentiation had not been fully understood.

PTH induction has been known to activate the cyclic adenosine monophosphate (cAMP) and protein kinase C (PKC) signaling pathways. Interestingly, the team found that in addition to PTH induction, activation of cAMP and PKC also resulted in overexpression of Gprc5a, albeit to a lesser extent, underscoring the potential involvement of other molecular pathways. Notably, upregulation of Gprc5a was suppressed upon inhibition of transcription, but, remained unaffected upon suppressing protein synthesis, suggesting that Gprc5a could be transcribed early on in response to PTH signaling and serves as a direct target gene.

Furthermore, the researchers examined the effect of Gprc5a downregulation on osteoblast proliferation and differentiation. Notably, while PTH induction alone did not affect cell proliferation, Gprc5a knockdown resulted in an increase in the expression of cell-cycle-related genes and osteoblast differentiation markers. These findings suggest that Gprc5a suppresses osteoblast proliferation and differentiation.

Diving deeper into the molecular mechanisms underlying the effects of Gprc5a, in PTH-induced osteogenesis, the researchers identified Activin receptor-like kinase 3 (ALK3) – a bone morphogenetic protein (BMP) signalling pathway receptor, as an interacting partner of Gprc5a. In line with their speculation, overexpression of Gprc5a indeed, led to suppression of BMP signalling via receptors including ALK3.

Overall, these findings reveal that Gprc5a – a novel inducible target gene of PTH, negatively regulates osteoblast proliferation and differentiation, by partially suppressing BMP signaling. Gprc5a can thus, be pursued as a novel therapeutic target while devising treatments against osteoporosis. The study sheds light on the complex process of bone remodeling and explains the bone-promoting and bone-resorbing effects of PTH signaling.

“Our study shows Gprc5a may function as a negative feedback factor for the bone formation promoting effect of teriparatide. Suppressing Gprc5a function may, therefore, increase the effectiveness of teriparatide in non-responding patients. In the future, we hope that our research will lead to improved quality of life and healthy longevity for people suffering from osteoporosis,” concludes Prof Hayata.

Source: Tokyo University of Science

How Stress Saps Cognitive Reserves, Increasing Dementia Risk

Photo by Alex Green on Pexels

While mentally stimulating activities and life experiences can improve cognition in memory clinic patients, stress undermines this beneficial relationship. This is according to a new study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Researchers in the late 1980s found that some individuals who showed no apparent symptoms of dementia during their lifetime had brain changes consistent with an advanced stage of Alzheimer’s disease. 

It has since been postulated that so-called cognitive reserve might account for this differential protective effect in individuals. 

Cognitively stimulating and enriching life experiences and behaviours such as higher educational attainment, complex jobs, continued physical and leisure activities, and healthy social interactions help build cognitive reserve. 

Increased risk of dementia

However, high or persistent stress levels are associated with reduced social interactions, impaired ability to engage in leisure and physical activities, and an increased risk of dementia.  

Researchers from Karolinska Institutet have now examined the association between cognitive reserve, cognition, and biomarkers for Alzheimer’s disease in 113 participants from the memory clinic at the Karolinska University Hospital, Huddinge, Sweden. 

They also examined how this association is modified by physiological stress (cortisol levels in saliva) and psychological (perceived) stress. 

Greater cognitive reserve was found to improve cognition, but interestingly, physiological stress appeared to weaken the association.  

“These results might have clinical implications as an expanding body of research suggests that mindfulness exercises and meditation may reduce cortisol levels and improve cognition,” says the study’s lead author Manasa Shanta Yerramalla, researcher at the Department of Neurobiology, Care Sciences and Society. “Different stress management strategies could be a good complement to existing lifestyle interventions in Alzheimer’s prevention.” 

The relatively small sample of participants reduces the possibility of drawing robust conclusions, but the results are generalisable to similar patient groups.  

Link between sleep and cognition 

Moreover, since stress disrupts sleep, which in turn disrupts cognition, the researchers controlled for sleeping medications; they did not, however, consider other aspects of sleep that might impair cognition. 

“We will continue to study the association between stress and sleeping disorders and how it affects the cognitive reserve in memory clinic patients,” says Dr Yerramalla. 

Source: Karolinska Institutet

First Menstrual Periods are Arriving Earlier for Younger Generations

Photo by Marta Branco

The average age at menarche, the first menstrual period, has been decreasing among younger generations in the US, especially those belonging to racial minorities and lower socioeconomic statuses, according to a new study led by researchers at Harvard T.H. Chan School of Public Health. It also found that the average time it takes for the menstrual cycle to become regular is increasing.

The study, published in JAMA Network Open, is the latest publication from the Apple Women’s Health Study, a longitudinal study of menstrual cycles, gynaecological conditions, and overall women’s health conducted by Harvard Chan School, the National Institute of Environmental Health Sciences, and Apple.

“Our findings can lead to a better understanding of menstrual health across the lifespan and how our lived environment impacts this critical vital sign,” said co-principal investigator Shruthi Mahalingaiah, assistant professor of environmental, reproductive, and women’s health at Harvard Chan School.

While previous studies have shown trends towards earlier menarche over the past five decades, data has been limited on how these trends present within different racial groups and socioeconomic statuses. Additionally, few studies have had sufficient data to identify any trends regarding time to menstrual cycle regularity.

The researchers used the Apple Women’s Health Study’s large, diverse dataset to fill this research gap. The 71 341 participants who enrolled between November 2018 and March 2023 self-reported the age at which they first began menstruating and their race and socioeconomic status. The researchers divided the participants into five age brackets: born between 1950–1969, 1970–1979, 1980–1989, 1990–1999, and 2000-2005. Ages of menarche were defined as early (younger than 11 years old), very early (younger than 9), and late (ages 16 and above). A subset of participants (61 932) self-reported the time it took for their menstrual cycle to become regular and were divided into five categories: up to two years, between three and four years, longer than five years, hasn’t become regular, or became regular with use of hormones. Another subset (9865) provided their body mass index (BMI) at their age of menarche.

The study found that as birth year increased (meaning younger participants), average age at menarche decreased and time from menarche to menstrual cycle regularity increased. Among participants born from 1950–1969, the average age at menarche was 12.5 years, and the rates of early and very early menarche were 8.6% and 0.6%, respectively. Among participants born from 2000–2005, the average age of menarche was 11.9 years, and the rates of early and very early menarche were 15.5% and 1.4%, respectively. Across the two groups, the percentage of participants who reached menstrual cycle regularity within two years of menarche decreased from 76% to 56%. The researchers observed that these trends were present among all sociodemographic groups but were most pronounced among the participants who identified as Black, Hispanic, Asian, or mixed race, and who rated themselves as belonging to a low socioeconomic status.

The findings showed that BMI at age of menarche could explain part of the trend toward periods starting earlier. Other possible factors that might explain the trend include dietary patterns, psychological stress and adverse childhood experiences, and environmental factors such as endocrine-disrupting chemicals and air pollution.

“Continuing to investigate early menarche and its drivers is critical,” said corresponding author Zifan Wang, postdoctoral research fellow in Harvard Chan School’s Department of Environmental Health. “Early menarche is associated with higher risk of adverse health outcomes, such as cardiovascular disease and cancer. To address these health concerns – which our findings suggest may begin to impact more people, with disproportionate impact on already disadvantaged populations – we need much more investment in menstrual health research.”

The authors noted some limitations to the study, including that it relies heavily on retrospective self-reporting.

Source: Harvard T.H. Chan School of Public Health

Women’s Mental Agility is Better During Their Periods

Photo by Ashley Williams

New research involving female football players has shown that they react more quickly and accurately during their periods, despite them feeling that they perform worse. The study, published in Neuropsychologia, is the first to assess sport-related cognition during the menstrual cycle and is part of a larger research project supported by the FIFA Research Scholarship.

The findings, from University College London, act as a proof-of-principle that specific types of cognition fluctuate throughout the menstrual cycle, which could have implications for injury and other aspects of women’s health.

Previous sports medicine research has shown that women seem to be at greater risk of sport-related injury during the luteal phase, which is the time between ovulation and menstruation. This is possibly related to the significant hormonal changes that occur throughout the menstrual cycle. But precisely how these changes are linked to an increased likelihood of injury are unknown at present.

In this study, researchers at UCL and ISEH collected reaction time and error data from 241 participants who completed a battery of cognitive tests 14 days apart. Participants also completed a mood scale and a symptom questionnaire twice. Period-tracking apps were used to estimate which phase of their cycle the participants were in when they took the tests.

The tests were designed to mimic mental processes that are typical in team sports. In one test, participants were shown smiling or winking faces and asked to press the space bar only when they saw a smiley face, to test inhibition, attention, reaction time and accuracy. In another, they were asked to identify mirror images in a 3D rotation task, which assesses spatial cognition. A task that asked them to click when two moving balls collide on screen measured spatial timing.

Though participants reported feeling worse during menstruation and perceived that this negatively impacted their performance, their reaction times were faster and they made fewer errors. For example, their timing was on average 10 milliseconds (12%) more accurate in the moving balls task, and they pressed the space bar at the wrong time 25% less in the inhibition task.

Participants’ reaction times were slower during the luteal phase, which begins after ovulation and lasts between 12–14 days up to the beginning of menstruation. They were on average 10–20 milliseconds slower compared to being in any other phase, but their error rate was unchanged.

Dr Flaminia Ronca, first author of the study from UCL Division of Surgery and Interventional Science and ISEH, said: “Research suggests that female athletes are more likely to sustain certain types of sports injuries during the luteal phase and the assumption has been that this is due to biomechanical changes as a result of hormonal variation. But I wasn’t convinced that physical changes alone could explain this association.

“Given that progesterone has an inhibitory effect on the cerebral cortex and oestrogen stimulates it, making us react slower or faster, we wondered if injuries could be a result of a change in athletes’ timing of movements throughout the cycle.

“What is surprising is that the participant’s performance was better when they were on their period, which challenges what women, and perhaps society more generally, assume about their abilities at this particular time of the month.

“I hope that this will provide the basis for positive conversations between coaches and athletes about perceptions and performance: how we feel doesn’t always reflect how we perform.”

To put the findings in context, the authors say the fluctuation in timing could be the difference between an injury or not. Previous research has shown that a variation of just 10 milliseconds can mean the difference between a concussion and a lesser injury, for example. In the colliding balls task, participants’ timing was on average 12 milliseconds slower during the luteal phase compared to every other phase, a difference of 16%.

Dr Megan Lowery, an author of the study from UCL Surgery & Interventional Science and ISEH, said: “There’s lots of anecdotal evidence from women that they might feel clumsy just before ovulation, for example, which is supported by our findings here. My hope is that if women understand how their brains and bodies change during the month, it will help them to adapt.

“Though there’s a lot more research needed in this area, these findings are an important first step towards understanding how women’s cognition affects their athletic performance at different points during their cycle, which will hopefully facilitate positive conversations between coaches and athletes around performance and wellbeing.”

Professor Paul Burgess, senior author of the study from UCL’s Institute of Cognitive Neuroscience, said: “This study emerged from listening carefully to female soccer players and their coaches. We created bespoke cognitive tests to try to mimic the demands made upon the brain at the points in the game where they were telling us that injuries and problems of timing occur at certain times of the menstrual cycle.

“As suggested by what the soccer players had told us, the data suggested that women who menstruate – whether they are athletes or not – do tend to vary in their performance at certain stages of the cycle. As a neuroscientist, I am amazed that we don’t already know more about this, and hope that our study will help motivate increasing interest in this vital aspect of sports medicine.”

Source: University College London

Scarring after Spinal Cord Injury is More Complex than Previously Thought

Fibrotic scar 14d after spinal cord injury, red – Col1a1+ perivascular fibroblast derived cells Photo: Daniel Holl

New research has found that scar formation after spinal cord injuries is more complex than previously thought. Scientists at Karolinska Institutet have identified two types of perivascular cells as key contributors to scar tissue, which hinders nerve regeneration and functional recovery. These findings, published in Natural Neuroscience, are also relevant for other brain and spinal cord injuries and could lead to targeted therapies for reducing scarring and improving outcomes.

The central nervous system (CNS) has very limited healing abilities. Injuries or autoimmune diseases like multiple sclerosis often lead to permanent functional deficits. 

Regardless of the injury’s cause, the body responds by forming a boundary around the damaged tissue, which eventually becomes permanent scar tissue. 

Two contributing cell types

While scar tissue seals the damaged area, it also prevents functional repair. After spinal cord injuries, scar tissue blocks the regeneration of nerve fibers that connect the brain with the body, resulting in paralysis after severe injuries.

The research team led by Christian Göritz at Karolinska Institutet has made significant progress in understanding how scar tissue forms in the CNS. The group now identified two distinct types of perivascular cells, which line different parts of blood vessels, as the major contributors to fibrotic scar tissue after spinal cord injury. Depending on the lesion’s location, the two identified cell types contribute differently.

“We found that damage to the spinal cord activates perivascular cells close to the damaged area and induces the generation of myofibroblasts, which consequently form persistent scar tissue,” explains first author Daniel Holl, researcher at the Department of Cell and Molecular Biology.

By examining the process of scar formation in detail, the researchers hope to identify specific therapeutic targets to control fibrotic scarring.